title: α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors.
abstract: Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting the existence of a local neural stem/progenitor cell niche. Here, we identify α-tanycytes as key components of a hypothalamic niche in the adult mouse. Long-term lineage tracing in vivo using a GLAST::CreER(T2) conditional driver indicates that α-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that α-tanycytes, but not β-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of α-tanycytes exist, amongst which only GFAP-positive dorsal α2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; α-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of α-tanycytes in vivo. Our results suggest that α-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation.
authors.affiliation: MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Robins
authors.forename: I
authors.initials: I
authors.lastname: Stewart
authors.forename: D E
authors.initials: DE
authors.lastname: McNay
authors.forename: V
authors.initials: V
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Giachino
authors.forename: M
authors.initials: M
authors.lastname: Goetz
authors.forename: J
authors.initials: J
authors.lastname: Ninkovic
authors.forename: N
authors.initials: N
authors.lastname: Briancon
authors.forename: E
authors.initials: E
authors.lastname: Maratos-Flier
authors.forename: J S
authors.initials: JS
authors.lastname: Flier
authors.forename: M V
authors.initials: MV
authors.lastname: Kokoeva
authors.forename: M
authors.initials: M
authors.lastname: Placzek
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D063928:Ependymoglial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D007150:Immunohistochemistry; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020542:Third Ventricle / Q000166:cytology*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D005904:Glial Fibrillary Acidic Protein; C493393:Slc1a3 protein, mouse; C113569:fibroblast growth factor 18; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; C045073:Cre recombinase; D019426:Integrases